Odor Experience Stabilizes Glomerular Output Representations in Two Mouse Models of Autism

Novel stimuli can be stressful for individuals with autism spectrum disorders (ASD), though repeated exposure can reduce this effect. In <i>Cntnap2^-/-</i> and <i>Shank3B^+/-</i> mouse models of ASD, novel background odors impaired behavioral target odor recognition but that deficit improved with training. To investigate the neural basis of this improvement, we used wide-field calcium imaging to measure olfactory bulb responses in <i>Cntnap2^-/-</i> and <i>Shank3B^+/-</i> mice and WT mice of either sex. Training with background odors enhanced both behavioral performance and neural discriminability of odor mixtures in both <i>Cntnap2^-/-</i> and <i>Shank3B^+/-</i> as well as WT mice. Naive <i>Cntnap2^-/-</i> and <i>Shank3B^+/-</i> mice showed greater trial-to-trial neural variability than WT mice, but training stabilized neural responses. Critically, training produced a widespread reduction in olfactory bulb responses to background odors in ASD models, but not in WT mice. Thus, despite similar behavioral improvements as WT mice, <i>Cntnap2^-/-</i> and <i>Shank3B^+/-</i> mice relied on a distinct broad suppression of background odor responses to enhance olfactory coding in the presence of background odors.